rs6906871

Variant names:

• chr6-136641079-C-A
• rs6906871
• NM_005923.4:c.1838+1441G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-136641079-C-A
• chr6-136641079-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005923.4(MAP3K5):​c.1838+1441G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 152,016 control chromosomes in the GnomAD database, including 24,570 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.56 (24570 hom., cov: 33)
• Consequence: MAP3K5 NM_005923.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.124
• Publications: 0 publications found

Genes affected

MAP3K5 (HGNC:6857): (mitogen-activated protein kinase kinase kinase 5) Mitogen-activated protein kinase (MAPK) signaling cascades include MAPK or extracellular signal-regulated kinase (ERK), MAPK kinase (MKK or MEK), and MAPK kinase kinase (MAPKKK or MEKK). MAPKK kinase/MEKK phosphorylates and activates its downstream protein kinase, MAPK kinase/MEK, which in turn activates MAPK. The kinases of these signaling cascades are highly conserved, and homologs exist in yeast, Drosophila, and mammalian cells. MAPKKK5 contains 1,374 amino acids with all 11 kinase subdomains. Northern blot analysis shows that MAPKKK5 transcript is abundantly expressed in human heart and pancreas. The MAPKKK5 protein phosphorylates and activates MKK4 (aliases SERK1, MAPKK4) in vitro, and activates c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) during transient expression in COS and 293 cells; MAPKKK5 does not activate MAPK/ERK. [provided by RefSeq, Jul 2008]

MAP3K5-AS1 (HGNC:40358): (MAP3K5 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005923.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K5	NM_005923.4	MANE Select	c.1838+1441G>T		intron	N/A	NP_005914.1
	MAP3K5	NM_001438058.1		c.2165+1441G>T		intron	N/A	NP_001424987.1
	MAP3K5	NM_001438579.1		c.1256+1441G>T		intron	N/A	NP_001425508.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K5	ENST00000359015.5	TSL:1 MANE Select	c.1838+1441G>T		intron	N/A	ENSP00000351908.4
	MAP3K5	ENST00000698928.1		c.2165+1441G>T		intron	N/A	ENSP00000514039.1
	MAP3K5-AS1	ENST00000432477.2	TSL:2	n.383+3977C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84834 AN: 151898 Hom.: 24572 Cov.: 33

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.762

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.584

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.558 AC: 84848 AN: 152016 Hom.: 24570 Cov.: 33 AF XY: 0.556 AC XY: 41293 AN XY: 74286

African (AFR) AF: 0.415 AC: 17199 AN: 41438

American (AMR) AF: 0.564 AC: 8621 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 2232 AN: 3468

East Asian (EAS) AF: 0.550 AC: 2843 AN: 5168

South Asian (SAS) AF: 0.708 AC: 3416 AN: 4826

European-Finnish (FIN) AF: 0.545 AC: 5752 AN: 10554

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.628 AC: 42693 AN: 67966

Other (OTH) AF: 0.576 AC: 1216 AN: 2112

Alfa AF: 0.583 Hom.: 3255

Bravo AF: 0.549

Asia WGS AF: 0.607 AC: 2109 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	11
DANN	Benign	0.62
PhyloP100		-0.12
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6906871; hg19: chr6-136962217; COSMIC: COSV62891741;